Zika virus infection during pregnancy causes brain abnormality in newborns, most remarkably small heads (microcephaly). Microcephaly is usually caused by defects in the development of the brain cortex. The brain cortex develops from the division, proliferation and differentiation of neuron precursors (neuroprogenitors). It is known that Zika virus can cause the depletion of neuroprogenitors and cell death, however, little is known about how this happens. Cholesterol is a fundamental lipid component that is essential for mammalian cell function and proliferation. Defects of cholesterol biosynthesis also causes microcephaly. Interestingly, host innate immune response to viral infection lead to production of interferons. While interferon can control viral infection, it also severely inhibits cholesterol biosynthesis. We propose that it was the innate anti-viral interferon response that causes a collateral damage to the developing brain during Zika virus infection. We plan to use animal models as well as stem cell technology to test our hypothesis. Our study may lead to new strategies to prevent microcephaly and other brain abnormalities associated with maternal Zika virus infection.